Host control of Trypanosoma brucei infections relies on adequate B cell mediated responses including anti-VSG antibody responses. Trypanotolerant animals, namely; Cape buffalo maintain anti-trypanosome specific antibody responses throughout infection. Studies in mice, however; show a failure to maintain adequate antibody responses to trypanosomes as well as a failure to generate subsequent specific responses to antigens. T. brucei infections in mice result in the loss of mature conventional B cell subsets presumed to be important in host control of the parasites including marginal zone B cells and follicular B cells. Mature cell subset losses are coupled with plasma cell expansion early during infection. Mature B cell pools are not replenished as there is a loss of transitional cells due in part to higher levels of apoptosis and a failure to replenish these cells from bone marrow. B1 B cells appear to constitute the majority of plasma cells and resist infection induced losses to a greater extant than B2 B cells.

The interaction between Ixodid ticks and their mammalian hosts is a complex relationship. While the mammalian host tries to avoid the completion of the feeding process, the tick has devised strategies to counteract these attempts. Tick saliva contains a vast array of pharmacological activities that presumably aid the tick to evade host responses, including anti-complement, oxidative and innate and adaptive immune responses. The characterization of these activities has gained momentum in the last several years. One of the best-studied activities present in tick saliva corresponds to the antigen known as Salp15, which inhibits TCR-mediated CD4+ T cell activation and IL-2 production. This study identifies CD4 as the specific receptor for Salp15 on T cells. A direct association occurs between CD4 and the C-terminal amino acids of Salp15, which allows Salp15 to act at the very beginning of TCR ligation-induced signaling cascades. Salp15 prevents the activation of Lck upon TCR engagement and the formation of lipid rafts and actin polymerization. Salp15 also affects tyrosine phosphorylation of several early signal components downstream of Lck, including Zap70, Lat, and PLCγ1. This study also demonstrates that the peptide that mediates the interaction of Salp15 with CD4, P11, is able to recapitulate the immunosuppressive activity of the whole saliva protein. These results clarify the molecular mechanisms of action of Salp15 on T cells and suggest that binding to CD4 is sufficient to elicit its immunosuppressive activity. The differentiation of Th17 cells requires the concerted action of IL-6 and TGFβ. However, the exact contribution of each cytokine has not been elucidated. This study also provides evidence indicating that the role of TGFβ during the differentiation of CD4+ T cells is exclusively the repression of IL-2 production, which has been shown to counteract the generation of these effector cells. The inhibition of IL-2 during the differentiation of CD4+ T cells mediated by Salp15 and the specific IP 3 receptor inhibitor 2-APB resulted in Th17 differentiation in vitro. Furthermore, the treatment of PLP139-151-immunized mice with Salp15 also resulted in increased differentiation of Th17 cells in the central nervous system and augmented pathology. Our results demonstrate that the role played by TFGβ is circumscribed to the inhibition of IL-2 during the differentiation of CD4+ T cells. Finally, this study shows that Salp15 inhibits the interaction between HIV-1 gp120 and CD4. Furthermore, Salp15 prevents the formation of syncitia of HL2/3 (a stable HeLa cell line expressing the envelop protein) and CD4-expressing cells. Salp15 prevented gp120-CD4 interaction at least partially through its direct interaction with the glycoprotein. A phage display library screen provided the interacting residues in the C1 domain of gp120. These results provide a potential basis to define exposed gp120 epitopes for the generation of neutralizing vaccines against HIV.

The Smyth line chicken (SL), an avian model for autoimmune vitiligo, is characterized by a postnatal loss of melanin pigmentation in feathers and the choroid of the eye. Earlier studies supported a hypothesis that an inherent pigment cell defect is necessary for the amelanosis which is the consequence of the selective destruction of melanocytes by the immune system. Data collected during the last decade has demonstrated that the MHC plays a major role in the development and severity of the SL vitiligo. The major objective of this study was to determine the factors contributing to the variable expression of the disease in the SL102 subline, selected by serotyping to be homozygous for the 102 MHC haplotype. The homogeneity of the MHC loci among SL102 and BL (parental control) birds was evaluated by serological, mixed lymphocyte response (MLR) and restriction fragment length polymorphism (RFLP) techniques. The results of these analyses were then studied in respect to their effects on the variation in incidence and severity of autoimmune vitiligo. All SL102 birds used in these studies appeared to carry the same, or nearly identical Ea-B haplotype as determined by serology as well as by MLR. Surprisingly, only 15 out of 22 BL birds were homozygous for Ea-B102, possibly due to a previous pedigreeing error. RFLP genotype assignment based on 4 different restriction enzymes and MHC class I and class II probes did not appear to have any influence on the incidence of vitiligo. No polymorphisms were found among SL102 birds using class II probe, while 2 RFLP genotypes were revealed with the class I probe. One of these loci was shown (P $<$.05) to be associated with the severity of the vitiligo. Peripheral blood lymphocytes obtained from the serologically haplotype matched SL, BL and an unrelated control (LBL) birds were analyzed for their mitogenic responses as well as their lymphocyte subset populations. SL102 birds had a higher proportion of CD4+ and CD8+ T-cells and a lower proportion of TCR1+ T-cells; but, they were also the poorer responder to a T-cell mitogen, ConA. One of the variant B-F RFLP polymorphisms was associated with a low ConA response, although these birds had a higher proportion of CD8+ T-cells than controls. From this study it is hypothesized that MHC class II locus is involved in the incidence of autoimmune vitiligo where as the severity of the disease is associated with MHC class I genes. The variation in mitogenic response and lymphocyte subset populations are possibly associated with subline differences that may not be MHC-related.

Rabbit HTLV-I transformed cell lines possessing diverse biological properties were derived in vitro from peripheral blood lymphocytes of New Zealand White rabbits. Two of the cell lines caused fatal leukemia with infiltration in the lungs, spleen, liver and kidneys of adult rabbit recipients within 10 days of inoculation. To determine whether cell lineage influences pathogenesis, the fatal leukemogenic cell lines were compared to those that cause benign chronic infection. Selected rabbit genes including TCR $\gamma$, TCR $\delta$, IL-2R$\alpha$ and CD8$\beta$ were cloned for use as probes for characterization of the lines. Although rabbit CD4+ and CD8+ $\alpha\beta$ T cells can be infected by HTLV-I, CD4-CD8-$\gamma\delta$ T cells predominated in our collection. Even though, the two HTLV-I lines with a leukemogenic effect were $\gamma\delta$ T cells, their lethal nature cannot be attributed solely to their lineage since other $\gamma\delta$ T cells failed to exhibit the same property. The dominance of HTLV-I $\gamma\delta$ T cell lines may be attributable to the high number of $\gamma\delta$ T cells in the rabbit peripheral blood. Since $\gamma\delta$ T cells predominate in rabbit HTLV-I infection, the primary structures of the rabbit TCR $\gamma$ and $\delta$ cDNA clones were determined. Exons 1 and 3 of both TCR $\gamma$ and $\delta$ shared a high degree of identity with their counterparts in other species. By contrast, exon 2 structures of both TCR $\gamma$ and TCR $\delta$ chains were highly divergent among species. Rabbit C$\gamma$ and C$\delta$ exon 2 lack a conserved cysteine residue thought to be responsible for disulfide bond between the TCR $\gamma$ and TCR $\delta$ chain. Two allelic forms of rabbit C$\delta$ were found. One allele has two copies of exon 2 arranged tandemly in the same orientation. Genomic sequence analysis revealed a 464 base pair insertion between C$\delta$ exons 1 and 3. The presence of a duplicate C$\delta$ exon 2 has not been reported for any other species. Availability of these cloned genes provides the groundwork for development of reagents specific for rabbit T cells.