This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peterson, K. E. Articles by Chesebro, B. Search for Related Content PubMed PubMed Citation Articles by Peterson, K. E. Articles by Chesebro, B.

Novel Role of CD8⁺ T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4⁺ Th1 Responses during Retrovirus Infection in Mice

Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 7 March 2002/ Accepted 24 April 2002

CD4⁺ Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8⁺ T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2^b allele at major histocompatibility complex (MHC) class II loci, a single H-2D^b MHC class I allele was sufficient for the development of a CD4⁺ Th1 response to FV. This effect of H-2D^b on CD4⁺ T-cell responses was dependent on CD8⁺ T cells, as demonstrated by depletion studies. A direct effect of CD8⁺ T-cell help in the development of CD4⁺ Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2^a/a mice induced FV-specific responses of H-2D^d-restricted CD8⁺ cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8⁺ T cells to naive H-2^a/a mice prior to infection resulted in the generation of FV-specific CD4⁺ Th1 responses. This novel helper effect of CD8⁺ T cells could be an important mechanism in the development of CD4⁺ Th1 responses following vaccinations that induce CD8⁺ CTL responses. The ability of MHC class I genes to facilitate CD4⁺ Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.

This article has been cited by other articles:

• Dace, D. S., Chen, P. W., Alizadeh, H., Niederkorn, J. Y. (2007). Ocular immune privilege is circumvented by CD4+ T cells, leading to the rejection of intraocular tumors in an IFN-{gamma}-dependent manner. J. Leukoc. Biol. 81: 421-429 [Abstract] [Full Text]  
• Kawabata, H., Niwa, A., Tsuji-Kawahara, S., Uenishi, H., Iwanami, N., Matsukuma, H., Abe, H., Tabata, N., Matsumura, H., Miyazawa, M. (2006). Peptide-induced immune protection of CD8+ T cell-deficient mice against Friend retrovirus-induced disease. Int Immunol 18: 183-198 [Abstract] [Full Text]  
• Zelinskyy, G., Robertson, S. J., Schimmer, S., Messer, R. J., Hasenkrug, K. J., Dittmer, U. (2005). CD8+ T-Cell Dysfunction due to Cytolytic Granule Deficiency in Persistent Friend Retrovirus Infection. J. Virol. 79: 10619-10626 [Abstract] [Full Text]  
• Chen, Q., Jackson, H., Parente, P., Luke, T., Rizkalla, M., Tai, T. Y., Zhu, H.-C., Mifsud, N. A., Dimopoulos, N., Masterman, K.-A., Hopkins, W., Goldie, H., Maraskovsky, E., Green, S., Miloradovic, L., McCluskey, J., Old, L. J., Davis, I. D., Cebon, J., Chen, W. (2004). Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant. Proc. Natl. Acad. Sci. USA 101: 9363-9368 [Abstract] [Full Text]  
• Uzonna, J. E., Joyce, K. L., Scott, P. (2004). Low Dose Leishmania major Promotes a Transient T Helper Cell Type 2 Response That Is Down-regulated by Interferon {gamma}-producing CD8+ T Cells. J. Exp. Med. 199: 1559-1566 [Abstract] [Full Text]  
• Klingel, K., Schnorr, J.-J., Sauter, M., Szalay, G., Kandolf, R. (2003). {beta}2-Microglobulin-Associated Regulation of Interferon-{gamma} and Virus-Specific Immunoglobulin G Confer Resistance Against the Development of Chronic Coxsackievirus Myocarditis. Am. J. Pathol. 162: 1709-1720 [Abstract] [Full Text]