Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.

Abstract

We have established a murine model system for exploring the ability of a CD4 subset-deficient host to cope with cytomegalovirus infection, and reported three findings. First, an antiviral response of the CD8 subset of T lymphocytes could be not only initiated but also maintained for a long period of time despite a continued absence of the CD4 subset, whereas the production of antiviral antibody proved strictly dependent upon help provided by the CD4 subset. Second, no function in the defense against infection could be ascribed as yet to CD4-CD8- T lymphocytes, which were seen to accumulate to a new subset as a result of depletion of the CD4 subset. This newly arising subset did not substitute for CD4+ T lymphocytes in providing help to B lymphocytes, and was also not effective in controlling the spread of virus in host tissues. As long as a function of these cells in the generation and maintenance of a CD8 subset-mediated response is not disproved, caution is indicated with concern to an autonomy of the CD8 subset. Third, even though with delay, the CD8+ effector cells raised in the CD4 subset-deficient host were able of clear vital tissues from productive infection and to restrict asymptomatic, persistent infection to acinar glandular epithelial cells in salivary gland tissue.

Adoptive transfer of cytomegalovirus‐specific effector CD4+T cells provides antiviral protection from murine CMV infection

“…Doses of 10 6 and 10 5 M38-specific CD8 + T cells provided antiviral protection in peripheral tissues of immunocompromised mice, whereas 10 4 M38-specific CD8 + T cells did not confer protection in any of the organs tested except in the spleen. Of note, none of the transferred doses of M38-specific CD8 + T cells could mediate protection in the salivary glands, further confirming previous findings of the crucial role of CD4 + T cells in mucosal immunity toward CMV in this particular tissue [15,16]. Next, to test whether the co-transfer of M25-specific CD4 + T cells with M38-specific CD8 + T cells would synergize in antiviral immunity, graded numbers of in vivo activated, FACS sorted M25-or M38-specific cells were transferred in combination or alone into sublethally irradiated mice, followed by MCMV infection (Fig.…”

Cutting Edge: Murine Cytomegalovirus Induces a Polyfunctional CD4 T Cell Response

“…1). The responses specific for peptides m18 872-886 , M25 409 -423 , m139 560 -574 , m141 [181][182][183][184][185][186][187][188][189][190][191][192][193][194][195] , and m142 24 -38 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . The sum of these individual responses represented ϳ1.5% of the total splenic CD4 T cells following MCMV infection.…”

“…Adoptive transfer of virus-specific CD8 T cells protects against CMVmediated disease in immunocompromised humans, and their maintenance requires human CMV-specific CD4 T cells (6). Similarly, the transfer of virus-specific CD8 T cells protects immunocompromised mice from disease (7), but acute MCMV infection is effectively controlled when CD8 T cells are absent in immunocompetent mice (3,8), highlighting a role for CD4 T cells in healthy mice.…”

“…In humans, CMV-specific CD4 T cells correlate with protection from disease (1), and CD4 T cells are required for control of mouse CMV (MCMV) 3 replication in the salivary gland and lung (2)(3)(4). The MCMV-specific Ab response is also dependent upon CD4 T cells and provides protection against recurrent, but not acute, infection (2,5). Adoptive transfer of virus-specific CD8 T cells protects against CMVmediated disease in immunocompromised humans, and their maintenance requires human CMV-specific CD4 T cells (6).…”

Persistent and Selective Deficiency of CD4+ T Cell Immunity to Cytomegalovirus in Immunocompetent Young Children

“…Primary CMV infection of neonates and infants usually results in continuous or frequent viral shedding into the urine and saliva for up to several years (3,4). In contrast, limited studies have indicated that adults with primary CMV infection stop continual viral shedding by 9 -12 mo after acquisition, and have only infrequent recurrences of shedding thereafter (8,9).…”