Reduced frequencies of polyfunctional CMV-specific T cell responses in infants with congenital CMV infection.

Abstract

PURPOSE:

CMV infection remains a priority for vaccine development. Vaccination of infants could modify congenital infection and provide lifetime immunity. Properties of CMV-specific T cells associated with control of viral replication in early life have not been fully defined.

METHODS:

CMV-specific CD4 and CD8 T cell responses were investigated in infants with congenital CMV infection and compared to adults with primary or chronic infection. PBMC were stimulated with UL83 (pp65) or UL122 (IE-2) peptide pools then stained with antibodies to markers of T cell subset (CD4 or CD8), phenotype (CD45RA, CCR7), or function (MIP1β, CD107, IFNγ, IL2) for flow cytometry analysis.

RESULTS:

Detection of CMV pp65-specific CD4 T cells was less common in infants than adults. Responder cells were primarily effector memory (EM, CD45RA-CCR7-) in adults, but mixed memory subsets in infants. Detection of CMV pp65-specific CD8 T cells did not differ between the groups, but infants had lower frequencies of total responding cells and of MIP1β- or CD107-expressing cells. Responder cells were EM or effector memory RA (CD45RA + CCR7-) in all groups. Polyfunctional T cells were less commonly detected in infants than adults. Responses to IE-2 were detected in adults but not infants. All infants had detectable circulating CMV DNA at initial study (versus 60 % of adults with primary infection) despite longer duration of CMV infection.

CONCLUSIONS:

Reduced frequencies and altered functional profile of CMV-specific CD4 and CD8 T cell responses were detected in infants compared to adults, and were associated with persistent CMV DNA in peripheral blood.

• Authors: Laura Gibson, Constance M Barysauskas, Margaret McManus, Sheryl Dooley, Daniele Lilleri, Donna Fisher, Tumul Srivastava, Don J Diamond, Katherine Luzuriaga
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 35 Issue 3 Pg. 289-301 (Apr 2015) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 25712611 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral

Topics

• Adult
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cytomegalovirus (genetics, immunology)
• Cytomegalovirus Infections (blood, congenital, immunology)
• DNA, Viral (blood)
• Humans
• Infant
• Infant, Newborn