Role of Cytokines in the Differentiation of CD4<sup>+</sup> T‐Cell Subsets <i>in vivo</i>

Coffman, Robert L.; Varkila, K; Scott, Phillip; Châtelain, R

doi:10.1111/j.1600-065x.1991.tb00611.x

Cited by 270 publications

(141 citation statements)

References 55 publications

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“…Previous reports demonstrated that treatment of.^r/Wmice with anii-IFN-7 exacerbated infection with L. major only when •ST/Wmice had received spleen cells from congenic BALB/c mice [25,26]. Our study confirms the results that removal of IFN--} had no elTect on the course of infection in .siiV/mice given a high dose of L. major.…”

Section: Discussionsupporting

confidence: 89%

Response ofscidmice to establishment ofLeishmania majorinfection

Guy

Belosevic

1995

Clinical and Experimental Immunology

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SUMMARYThe initiation o^ Leishmania major \n^e:c\\ox\ in su.sceptible BALB/c mice is regulated by inlerferongamma (lKN-->). To examine further the mechanisms of lFN-7-dependent regulation of the establishment of L. major, we studied the characteristics of the infection in severe combined immunodeticient {scid) mice. In the lirst 2 weeks of infection, we observed a delay in the development of the lesions in the footpads and lower numbers of parasites in scid compared with BALB/c mice. By week 5 after infection, the size ofthe leishmanial lesion was similar in both strains of mice, but the number of parasites in scid mice was 100-fold higher than in BALB/c. Treatment with anti-IFN-7 during the establishment of L. major did not alter the course of infection in .Wi^mice, while it exacerbated lesion development in BALB/c mice. Macrophages from scid mice were unable to kill L. major when stimulated with IFN--) in vitro, and produced lower levels of nitric oxide compared with macrophages from susceptible BALB/c or the resistant C57B1/ 6 mice. We examined whether delayed lesion development in.«((/mice was due to their inability to mouni appropriate inflammatory responses. While significantly fewer nucleated cells were present in the footpads of .vc/J mice compared with BALB/c. 2 and 3 weeks alter infection, no difference in inflammatory response between scid and BALB/c mice was observed in response to L. major antigen in the footpads. In contrast, there was a dramatic increase in the number ofcells in ihe popliteal lymph nodes of BALB/c mice. Decreased inflammatory responses oWscid mice in Ihe footpad (at (he site of infection) may contribute to slower development of leishmanial lesions during the first 2 weeks of infection.

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Section: Discussionsupporting

confidence: 89%

Response ofscidmice to establishment ofLeishmania majorinfection

Guy

Belosevic

1995

Clinical and Experimental Immunology

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“…IL-4 supports IgG1 and IgE Ab production and generation; hence, the low levels of anti-OVA IgG1 and IgE Abs were consistent with the observed cytokine profiles (i.e., IL-2, IFN-␥, IL-5, and IL-6) of the OVA-restimulated CD4 ϩ T cells of RANTES-treated mice (37)(38)(39). IFN-␥ production is often associated with IgG2a and IgG3 Ab production (40) and may account for the RANTES-mediated anti-OVA IgG2a and IgG3 Ab responses. Even low doses of IFN-␥ (1,500 U) have been shown to increase IgG2a production in vivo, while considerably FIGURE 2.…”

Section: Discussionmentioning

confidence: 99%

RANTES Potentiates Antigen-Specific Mucosal Immune Responses

Lillard

Boyaka

Taub

et al. 2001

The Journal of Immunology

106

105

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RANTES is produced by lymphoid and epithelial cells of the mucosa in response to various external stimuli and is chemotactic for lymphocytes. The role of RANTES in adaptive mucosal immunity has not been studied. To better elucidate the role of this chemokine, we have characterized the effects of RANTES on mucosal and systemic immune responses to nasally coadministered OVA. RANTES enhanced Ag-specific serum Ab responses, inducing predominately anti-OVA IgG2a and IgG3 followed by IgG1 and IgG2b subclass Ab responses. RANTES also increased Ag-specific Ab titers in mucosal secretions and these Ab responses were associated with increased numbers of Ab-forming cells, derived from mucosal and systemic compartments. Splenic and mucosally derived CD4+ T cells of RANTES-treated mice displayed higher Ag-specific proliferative responses and IFN-γ, IL-2, IL-5, and IL-6 production than control groups receiving OVA alone. In vitro, RANTES up-regulated the expression of CD28, CD40 ligand, and IL-12R by Ag-activated primary T cells from DO11.10 (OVA-specific TCR-transgenic) mice and by resting T cells in a dose-dependent fashion. These studies suggest that RANTES can enhance mucosal and systemic humoral Ab responses through help provided by Th1- and select Th2-type cytokines as well as through the induction of costimulatory molecule and cytokine receptor expression on T lymphocytes. These effects could serve as a link between the initial innate signals of the host and the adaptive immune system.

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“…Salmonella serovars are facultative parasites that are capable of surviving and persisting within mammalian host cells and Th1-type response is essential for control of such intracellular pathogens [46]. IL-12 and IFN-␥ are thought to be important for induction of Th1 response mediated by ␣␤ T cells [47]. IL-15 has been recently reported to up-regulate IL-12R␤1 expression on T cells [45].…”

Section: Discussionmentioning

confidence: 99%